Tetrahydrofuran → Ethyl [({[1-({[(3R)-2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]amino}carbonyl)piperidin-4-yl]amino}carbonyl)amino](pyridin-2-yl)acetate

Participants

Reaction Steps

(3R)-3-Amino-5-phenyl-1-(2,2,2-trifluoroethyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one (90 mg, 0.270 mmol) (Y.-J. Shi et al., Tetrahedron, 1999, 55, 909-918) and triethylamine (37 uL, 0.270 mmol) in tetrahydrofuran (3 mL) were added to a solution of p-nitrophenylchloroformate (54 mg, 0.270 mmol) in tetrahydrofuran (15 mL) at 0° C. After 1 h, additional triethylamine (74 uL, 0.540 mmol) and ethyl {[(piperidin-4-ylamino)carbonyl]amino}(pyridin-2-yl)acetate (100 mg, 0.598 mmol) in tetrahydrofuran (5 μL) and dimethyl formamide (1 mL) were added and stirred at 0 oC for 10 min and then warmed to room temperature. After 4 h, the reaction was concentrated and the residue dissolved in ethyl acetate, washed with 1 N sodium hydroxide solution (3×), water, brine, and dried over magnesium sulfate. Purification by silica gel chromatography (100% dichloromethane→12% methanol/dichloromethane) gave 70 mg of the titled compound.

Provenance & Evidence